Quercetin regulates the inhibitory effect of monoclonal non-specific suppressor factor β on tumor necrosis factor-α production in LPS-stimulated macrophages

Monoclonal non-specific suppressor factor 0 (MNSF beta) is a member of the ubiquitin-like family that has been implicated in various biological functions. Previous studies have demonstrated that MNSF beta regulates the ERK1/2-MAPK cascade in the macrophage cell line Raw 264.7. In this study, we found evidence that the flavonol quercetin regulates the effect of MNSF beta on TNF alpha production in LPS-stimulated Raw264.7 cells. Quercetin inhibited MNSF beta siRNA-mediated enhancement of both TNFa production and ERK1/2 phosphorylation in LPS-stimulated Raw264.7 cells. Quercetin decreased the expression of 33.5-kDa MNSF beta adduct, which is important to the regulation of ERK1/2 activity, in unstimulated Raw264.7 cells. The various flavonoids tested, including other flavonols, did not affect the formation of this adduct. Collectively, MNSF beta and quercefin might share a common pathway in regulating the ERK1/2 pathway in macrophages. This is the first report describing the involvement of flavonoids in the action of ubiquitin-like proteins.